Bile acid metabolism and signaling in liver disease

Bile acids (BAs) have signaling functions efficiently regulating their own metabolism and transport as well as key aspects of lipid and glucose homeostasis. BAs shape the gut microbial flora and conversely are metabolized by microbiota. Disruption of BA transport, metabolism and physiological signaling function contribute to the pathogenesis and progression of a wide range of liver diseases including cholestatic disorders and metabolic dysfunction-associated steatotic liver disease (MASLD) as well as hepatocellular and cholangiocellular carcinoma. Additionally, impaired BA signaling may also affect the intestine and kidney, thereby contributing to failure of gut integrity driving the progression and complications of portal hypertension, cholemic nephropathy and the development of extrahepatic malignancies such as colorectal cancer. This review will summarize recent advances in the understanding of BA signaling, metabolism and transport focusing on transcriptional regulation and novel BA-focused therapeutic strategies for cholestatic and metabolic liver diseases.